Impact of residual microcalcifcations on prognosis after neoadjuvant chemotherapy in breast cancer patients.

BACKGROUND: Residual microcalcifications after neoadjuvant chemotherapy (NAC) are challenging for deciding extent of surgery and questionable for impact on prognosis. We investigated changes in the extent and patterns of microcalcifications before and after NAC and correlated them with pathologic response. We also compared prognosis of patients depending on presence of residual microcalcifications after NAC. METHODS: A total of 323 patients with invasive breast carcinoma treated with neoadjuvant chemotherapy at Kangbuk Samsung Hospital and Samsung Medical center from March 2015 to September 2018 were included. Patients were divided into four groups according to pathologic response and residual microcalcifications. Non-pCRw/mic group was defined as breast non-pCR with residual microcalcifications. Non-pCRw/o mic group was breast non-pCR without residual microcalcifications. pCRw/mic group was breast pCR with residual microcalcifications. pCRw/o mic group was breast pCR without residual microcalcifications. The first aim of this study is to investigate changes in the extent and patterns of microcalcifications before and after NAC and to correlate them with pathologic response. The second aim is to evaluate oncologic outcomes of residual microcalcifications according to pathologic response after NAC. RESULTS: There were no statistical differences in the extent, morphology, and distribution of microcalcifications according to pathologic response and subtype after NAC (all p > 0.05). With a median follow-up time of 71 months, compared to pCRw/o mic group, the hazard ratios (95% confidence intervals) for regional recurrence were 5.190 (1.160-23.190) in non-pCRw/mic group and 5.970 (1.840-19.380) in non-pCRw/o mic group. Compared to pCRw/o mic group, the hazard ratios (95% CI) for distant metastasis were 8.520 (2.130-34.090) in non-pCRw/mic group, 9.120 (2.850-29.200) in non-pCRw/o mic group. Compared to pCRw/o mic, the hazard ratio (95% CI) for distant metastasis in pCRw/mic group was 2.240 (0.230-21.500) without statistical significance (p = 0.486). CONCLUSIONS: Regardless of residual microcalcifications, patients who achieved pCR showed favorable long term outcome compared to non-pCR group.

Association between skeletal muscle mass and mammographic breast density.

Mammographic density (MD) of the breast and body mass index (BMI) are inversely associated with each other, but have inconsistent associations with respect to the risk of breast cancer. Skeletal muscle mass index (SMI) has been considered to reflect a relatively accurate fat and muscle percentage in the body. So, we evaluated the relation between SMI and MD. A cross-sectional study was performed in 143,456 women who underwent comprehensive examinations from 2012 to 2016. BMI was adjusted to analyze whether SMI is an independent factor predicting dense breast. After adjustment for confounding factors including BMI, the odds ratios for MD for the dense breasts was between the highest and lowest quartiles of SMI at 2.65 for premenopausal women and at 2.39 for postmenopausal women. SMI was a significant predictor for MD, which could be due to the similar growth mechanism of the skeletal muscle and breast parenchymal tissue. Further studies are needed to understand the causal link between muscularity, MD and breast cancer risk.

Clinical Outcomes Following Letrozole Treatment according to Estrogen Receptor Expression in Postmenopausal Women: LETTER Study (KBCSG-006).

PURPOSE: In this trial, we investigated the efficacy and safety of adjuvant letrozole for hormone receptor (HR)-positive breast cancer. Here, we report the clinical outcome in postmenopausal women with HR-positive breast cancer treated with adjuvant letrozole according to estrogen receptor (ER) expression levels. METHODS: In this multi-institutional, open-label, observational study, postmenopausal patients with HR-positive breast cancer received adjuvant letrozole (2.5 mg/daily) for 5 years unless they experienced disease progression or unacceptable toxicity or withdrew their consent. The patients were stratified into the following 3 groups according to ER expression levels using a modified Allred score (AS): low, intermediate, and high (AS 3-4, 5-6, and 7-8, respectively). ER expression was centrally reviewed. The primary objective was the 5-year disease-free survival (DFS) rate. RESULTS: Between April 25, 2010, and February 5, 2014, 440 patients were enrolled. With a median follow-up of 62.0 months, the 5-year DFS rate in all patients was 94.2% (95% confidence interval [CI], 91.8-96.6). The 5-year DFS and recurrence-free survival (RFS) rates did not differ according to ER expression; the 5-year DFS rates were 94.3% and 94.1%in the low-to-intermediate and high expression groups, respectively (p = 0.6), and the corresponding 5-year RFS rates were 95.7% and 95.4%, respectively (p = 0.7). Furthermore, 25 patients discontinued letrozole because of drug toxicity. CONCLUSION: Treatment with adjuvant letrozole showed very favorable treatment outcomes and good tolerability among Korean postmenopausal women with ER-positive breast cancer, independent of ER expression. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01069211.

Mammographic breast density, its changes, and breast cancer risk in premenopausal and postmenopausal women.

BACKGROUND: The risk of breast cancer related to changes in breast density over time, including its regression and persistence, remains controversial. The authors investigated the relationship between breast density and its changes over time with the development of breast cancer in premenopausal and postmenopausal women. METHODS: The current cohort study included 74,249 middle-aged Korean women (aged ≥35 years) who were free of breast cancer at baseline and who underwent repeated screening mammograms. Mammographic breast density was categorized according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS). A dense breast was defined as heterogeneously dense or extremely dense, and changes in dense breasts between baseline and subsequent follow-up were classified as none, developed, regressed, or persistent dense breast. RESULTS: During a median follow-up of 6.1 years (interquartile range, 4.1-8.8 years), a total of 803 incident breast cancers were identified. Baseline breast density was found to be positively associated with incident breast cancer in a dose-response manner, and this association did not significantly differ by menopausal status. The multivariable-adjusted hazard ratios (HRs) for breast cancer comparing "heterogeneously dense" and "extremely dense" categories with the nondense category were 1.96 (95% confidence interval [95% CI], 1.40-2.75) and 2.86 (95% CI, 2.04-4.01), respectively. With respect to changes in dense breasts over time, multivariable-adjusted HRs for breast cancer comparing persistent dense breast with none were 2.37 (95% CI, 1.34-4.21) in premenopausal women and 3.61 (95% CI, 1.78-7.30) in postmenopausal women. CONCLUSIONS: Both baseline dense breasts and their persistence over time were found to be strongly associated with an increased risk of incident breast cancer in premenopausal and postmenopausal women. LAY SUMMARY: Both baseline breast density and its changes over time were found to be independently associated with the risk of breast cancer in both premenopausal and postmenopausal women. The risk of incident breast cancer increased in women with persistent dense breasts, whereas the breast cancer risk decreased as dense breasts regressed. The findings of the current study support that both dense breasts at baseline and their persistence over time are independent risk factors for developing breast cancer.

Menopausal Transition, Body Mass Index, and Prevalence of Mammographic Dense Breasts in Middle-Aged Women.

The interrelationship between menopausal stage, excessive adiposity and dense breasts remains unclear. We aimed to investigate the relationship between menopausal stage and dense-breast prevalence in midlife women while considering a possible effect modification of being overweight. The present cross-sectional study comprised 82,677 Korean women, aged 35-65 years, who attended a screening exam. Menopausal stages were categorized based on the Stages of Reproductive Aging Workshop (STRAW + 10) criteria. Mammographic breast density was categorized according to Breast Imaging Reporting and Data System (BI-RADS). Dense breasts were defined as BI-RADS Breast Density category D (extremely dense). The prevalence of dense breasts decreased as menopausal stage increased (p-trend < 0.001), and this pattern was pronounced in overweight women than non-overweight women (p-interaction = 0.016). Compared with pre-menopause, the multivariable-adjusted prevalence ratios (and 95% confidence intervals) for dense breasts were 0.98 (0.96-1.00) in early transition, 0.89 (0.86-0.92) in late transition, and 0.55 (0.52-0.59) in post-menopause, among non-overweight women, while corresponding prevalence ratios were 0.92 (0.87-0.98), 0.83 (0.77-0.90) and 0.36 (0.31-0.41) among overweight women. The prevalence of dense breasts was inversely associated with increasing menopausal stages and significantly decreased from the late menopausal transition, with stronger declines among overweight women.

Predictive factors for the presence of invasive components in patients diagnosed with ductal carcinoma in situ based on preoperative biopsy.

BACKGROUND: In patients diagnosed with ductal carcinoma in situ (DCIS) with needle biopsy before surgery, invasive component (IC) is often found in the postoperative tissue, which results in altered post-surgical care. However, there are no clinically available factors to predict IC, and few MRI studies are available for the detection of IC in DCIS patients. The purpose of this study was to evaluate which risk factors can predict IC preoperatively. METHODS: Patients with a DCIS diagnosis based on preoperative biopsy, who underwent breast surgery Kangbuk Samsung Hospital between Jan 2005 and June 2018, were retrospectively evaluated. Clinico-pathological and breast MRI factors were compared between DCIS and DCIS with IC in postsurgical specimens. RESULTS: Of the 431 patients with a preoperative diagnosis of DCIS, 34 (7.9%) showed IC during the postoperative pathological investigations, and 217 (50.3%) underwent breast MRI. Among MRI-related factors, Mass-like enhancement on MRI was the sole but significant predictor of IC (HR = 0.26, C.I. = 0.07-0.93, p = 0.038), while nipple-areolar complex invasion, enhancement peak and pattern were not statistically significant. Nuclear grade was the only significant predictor of IC in the analysis of other clinico-pathological factors (HR = 2.39, C.I. = 1.05-5.42, p = 0.038 in univariate analysis, HR = 2.86, C.I. = 1.14-7.14, p = 0.025 in multivariate analysis). CONCLUSIONS: Mass-like enhancement on MRI and high nuclear grade were associated with IC in patients with preoperative diagnosis of DCIS. Considering the high sensitivity of breast MRI for IC, further evaluation of the predictive value of MRI in preoperative DCIS patients is desirable.

Serum concentration of thyroid hormones in abnormal and euthyroid ranges and breast cancer risk: A cohort study.

The impact of variations in serum thyroid hormone concentration within the euthyroid range on breast cancer risk remains unclear. We investigated the effect of serum thyrotropin (TSH) and thyroid hormone concentration on breast cancer risk. This cohort study involved 62,546 Korean women, aged ≥40 years, who were free of breast cancer at baseline and underwent health examination with determination of free thyroxine (FT4) and TSH. A parametric proportional hazard model was used to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI). During a median follow-up of 4.8 years (interquartile range: 2.8-7.3 years), 834 incident breast cancers were identified. Compared to normal FT4 level, abnormally high serum FT4 level was associated with an increased risk of incident breast cancer with a corresponding multivariable aHR (95% CI) of 1.98 (1.02-3.83). This association tended to be stronger in postmenopausal women than in premenopausal women. Within the euthyroid range, the highest TSH tertile was associated with a lower risk of breast cancer than the lowest TSH tertile with a corresponding aHR (95% CI) of 0.68 (0.55-0.84). In contrast, highest FT4 tertile was associated with a higher risk of breast cancer than the lowest FT4 tertile. Abnormally high FT4 as well as higher FT4 within the euthyroid range were positively associated with breast cancer risk, while higher TSH concentration within the euthyroid range was negatively associated with breast cancer risk. Our findings indicate that thyroid function within both the abnormal and euthyroid ranges may contribute to the development of breast cancer.

Different prognostic values of individual hematologic parameters in papillary thyroid cancer due to age-related changes in immunity.

PURPOSE: Several studies have reported the plausible association of neutrophil-to-lymphocyte ratio (NLR) with the prognosis of papillary thyroid cancer (PTC), but the results are inconsistent. In PTC, chronic inflammation is closely related to tumor progression, and the age of the patient has a great influence on prognosis. Therefore, considering the changes in the immune system with aging, we classified the patients according to age and assessed the prognostic value of individual hematologic parameters. METHODS: This retrospective analysis included 1,921 patients who underwent thyroidectomy for PTC. Patients were divided into 2 groups based on their age: Y-group (age < 45) and O-group (age ≥ 45). Blood counts were measured within 14 days before surgery. RESULTS: The Y-group consisted of 914 patients aged < 45 years and the O-group consisted of 932 patients aged ≥ 45. In both groups, the common prognostic factors related to disease recurrence were only 6 or more metastatic lymph node and grossly extrathyroidal extension, and hematologic parameters were different between the 2 groups. High Platelet-lymphocyte ratio (PLR) in the Y-group and high NLR in the O-group were identified as independent predictors of disease recurrence (NLR: hazard ratio [HR], 3.28; 95% confidence interval [CI], 1.23-8.73; P = 0.018; PLR: HR, 3.08; 95% CI, 1.26-7.52; P = 0.014). CONCLUSION: The results suggest that changes in immunity with aging may affect prognosis in patients with PTC, and thus hematologic parameters might be employed as prognostic markers depending on the age of the patients.

The prognostic and predictive value of tumor-infiltrating lymphocytes and hematologic parameters in patients with breast cancer.

BACKGROUND: Carcinogenesis and tumor growth are associated with chronic inflammation and the host immune system. Here, we investigated the clinical significance and relationship between tumor-infiltrating lymphocytes (TILs) and hematologic parameters in patients with breast cancer. METHODS: Invasive ductal breast cancer patients (N = 145) who underwent surgery were retrospectively evaluated. Samples were obtained using a core needle biopsy for CD8+, FOXP3+ TIL assessment. Blood lymphocytes, neutrophils, monocytes, and platelets were obtained by peripheral venous punctures. RESULTS: CD8 + TILs were significantly associated with absolute lymphocyte count (ALC) and the absolute monocyte count (AMC). Low LMR (ALC/AMC) (cut-off - 5.3, range = 0.73-12.31) was associated with poor overall survival (OS) (p = 0.010), disease-free survival (DFS) (p = 0.005). However, in subgroup analysis, LMR did not have any value as a prognostic factor in HER2-positive breast cancers. TILs had different prognostic impacts across breast cancer subtypes, although they were not statistically significant. The treatment response after NAC tended to improve in breast cancer patients with high FOXP3+ TILs, low NLR (neutrophil count/ALC) (FOXP3 p for trend = 0.006, NLR p for trend = 0.063). CONCLUSIONS: A relevance between TILs and hematologic parameters in breast cancer was demonstrated. The influence of the immune system on breast cancer progression may differ by subtype.

Prognostic significance of expression of epithelial-mesenchymal transition driver brachyury in breast cancer and its association with subtype and characteristics.

Brachyury is a T-box transcription factor characterized as a driver of the epithelial-to-mesenchymal process, which is associated with poor prognosis of patients with breast cancer. The present study investigated expression of brachyury in breast cancer including primary tumor, metastatic and recurred tumor tissues, and the clinical significance and value of brachyury as a prognostic biomarker. This retrospective study included a series of 102 consecutive patients surgically resected between January 2005 and December 2011. Brachyury expression in tumor cell was evaluated using immunohistochemistry and scored as the immunoactivity. Of 102 patients, 62 primary tumors were positive for brachyury expression and 40 were negative. Multivariate analysis of disease-free survival (DFS) revealed brachyury expression, HER2 and lymphovascular invasion as independent prognostic factors [brachyury negative vs. positive hazard ratio (HR), 3.0; P=0.024; HER2 negative vs. positive HR, 4.9; P=0.003; lymphovascular invasion absent vs. present HR, 3.5; P=0.020]. These results were particularly observed in triple-negative breast cancer (TNBC), no recurrence or mortality occurred in brachyury negative group during the follow-up period, and therefore a significantly improved prognosis was demonstrated in these patients compared with the brachyury positive group [overall survival (OS), P=0.022; DFS, P=0.002]. Brachyury expression in metastatic lymph node/recurred tumors was not significantly associated with prognosis (OS, P=0.745; DFS, P=0.189). Therefore, Brachyury expression in primary tumor independently is a potential predictor of poor prognosis, particularly in TNBC, where it appears to serve a crucial function in recurrence and mortality. Brachyury vaccines under clinical trials are likely to be useful in patients with breast cancer.

Feasibility of Preoperative Axillary Lymph Node Marking with a Clip in Breast Cancer Patients Before Neoadjuvant Chemotherapy: A Preliminary Study.

BACKGROUND: The aim of this study was to determine the feasibility of image-guided marker-clip placement in axillary lymph nodes (ALNs) for breast cancer upon initial presentation and to assess the reliability of this method with sentinel lymph node biopsy (SLNB) for axillary restaging after neoadjuvant chemotherapy (NAC). METHODS: Between June 2015 and August 2016, a marker clip was placed at a clinically positive ALN under ultrasonography (US) guidance before initiation of NAC in 20 patients. Preoperative localization of marker-clipped LNs was performed, and the localized LNs were removed by SLNB. We compared the postoperative results of the marker-clipped LNs, SLNs and ALNs. RESULTS: Image-guided marker-clip placements and localization of marker-clipped LNs were performed successfully in 20 patients. A total of 24 marker clips were inserted, and 23 marker-clipped LNs were successfully retrieved during surgery (identification rate, 23/24, 95.8%). In the 11 patients with pathologically confirmed metastatic marker-clipped LNs, four became negative after NAC, and seven maintained metastatic residues on the marker-clipped LNs. Three of the seven patients had metastatic residues on the ALNs, and two of the three patients also had negative SLNs. Marker-clipped nodes accurately predicted the axillary nodal status in these two patients compared with SLNs alone. CONCLUSION: Image-guided marker-clip placement on positive ALNs before NAC and removal with SLNB is technically feasible. This technique can improve the accuracy of the residual disease evaluation on the axilla, especially in patients with negative SLNB results, and can identify candidates for limited axillary surgery after NAC.

Diagnostic Value of Contrast-Enhanced Digital Mammography versus Contrast-Enhanced Magnetic Resonance Imaging for the Preoperative Evaluation of Breast Cancer.

PURPOSE: This study aimed to compare the diagnostic performance of contrast-enhanced digital mammography (CEDM) and contrast-enhanced magnetic resonance imaging (CEMRI) in preoperative evaluations, and to evaluate the effect of each modality on the surgical management of women with breast cancer. METHODS: This single-center, prospective study was approved by the Institutional Review Board, and informed consent was obtained from all patients. From November 2016 to October 2017, 84 patients who were diagnosed with invasive carcinoma (69/84) and ductal carcinoma in situ (15/84), and underwent both CEDM and CEMRI, were enrolled. Imaging findings and surgical management were correlated with pathological results and compared. The diagnostic performance of both modalities in the detection of index and secondary cancers (multifocality and multicentricity), and occult cancer in the contralateral breast, was compared. The authors also evaluated whether CEDM or CEMRI resulted in changes in the surgical management of the affected breast due to imaging-detected findings. RESULTS: Eighty-four women were included in the analysis. Compared with CEMRI, CEDM demonstrated a similar sensitivity (92.9% [78/84] vs. 95.2% [80/84]) in detecting index cancer (p=0.563). For the detection of secondary cancers in the ipsilateral breast and occult cancer in the contralateral breast, no significant differences were found between CEDM and CEMRI (p=0.999 and p=0.999, respectively). Regarding changes in surgical management, CEDM resulted in similar changes compared with CEMRI (30.9% [26/84] vs. 29.7% [25/84], p=0.610). Regarding changes in surgical management due to false-positive findings, no significant differences were found between CEDM and CEMRI (34.6% [9/26] vs. 44.0% [11/25], p=0.782). CONCLUSION: CEDM demonstrated a diagnostic performance comparable with CEMRI in depicting index cancers, secondary cancers, and occult cancer in the contralateral breast. CEDM demonstrated similar changes in surgical management compared with CEMRI.

Assessing cosmetic results after conventional thyroidectomy using the EASY-EYE_C: a double-blind randomized controlled trial.

PURPOSE: The incidence of thyroid cancer is relatively high, especially in young women, and postoperative scarring after thyroidectomy is an important problem for both patients and clinicians. Currently, there is no available product that can be used for wound protection during thyroid surgery. We used the EASY-EYE_C, a new silicone-based wound protector. METHODS: We conducted a double-blind randomized controlled trial to assess the efficacy of the EASY-EYE_C with surgical scars. We studied 66 patients who underwent conventional total thyroidectomy or hemithyroidectomy performed by a single surgeon from August 2015 to June 2016. At 6-week follow-up, a single blinded physician observed the wounds to make clinical assessments using the Patient and Observer Scar Assessment Scale (POSAS), the Vancouver Scar Scale (VSS), and a modified Stony Brook Scar Evaluation Scale (SBSES). RESULTS: There were no significant differences by sex, age, type of surgery, body mass index, length of wound, incision site (from sternal notch), or thyroid weight, but the duration of operation was significantly shorter in the experimental group (E group). The e-group also had better POSAS scores than the control group (C group), with means of 43.2 (standard deviation [SD], ±15.9) versus 68.3 (SD, ±21.5), respectively (P < 0.05). The modified SBSES and VSS scores were similar to those from the POSAS. CONCLUSION: In this study, all scores for evaluating outcomes were higher in the E group than in the C group. In addition, the operation time was significantly shorter in the E group. Therefore, the EASY-EYE_C may be useful for improving the cosmetic outcomes of conventional thyroid surgery.

Expression of epithelial-mesenchymal transition driver brachyury and status of tumor-infiltrating CD8+ and FOXP3+ lymphocytes in predicting treatment responses to neoadjuvant chemotherapy of breast cancer.

Brachyury has been characterized as a driver of epithelial-mesenchymal transition process which is regarded as an important mechanism of cancer cell invasion and metastatic progression. The status of tumor-infiltrating lymphocytes has been proposed to predict response to neoadjuvant chemotherapy in breast cancer. We investigated the clinical significance and value of tumor-infiltrating lymphocytes and brachyury as biomarkers to predict treatment responses to neoadjuvant chemotherapy in breast cancer. We also examined the correlation of the Neo-Bioscore with tumor-infiltrating lymphocytes and brachyury to indirectly predict long-term outcome. This retrospective study included a series of 44 consecutive patients treated between January 2011 and December 2015. All patient samples were obtained using core needle biopsy before neoadjuvant chemotherapy. The relationship of expression of Brachyury and tumor-infiltrating lymphocyte subsets (CD8+, forkhead box protein 3 tumor-infiltrating lymphocytes) with clinicopathological factors was assessed to identify its predictive role with respect to tumor response to neoadjuvant chemotherapy and the outcome. Of 44 patients, 6 showed no response, 31 had partial response, and 7 demonstrated pathological complete response. Forkhead box protein 3 was significantly higher in the response group than in the no response group (no response = 2.6, partial response = 7.0, complete response = 9.7, p = 0.020). Brachyury expression was inversely associated with response to neoadjuvant chemotherapy, but the difference was not statistically significant ( p = 0.62). We also observed a significant association between forkhead box protein 3 ( p = 0.001) and the Neo-Bioscore, while only a marginal difference was observed with CD8+ expression ( p = 0.074). This study demonstrated that forkhead box protein 3 expression has value as the only independent marker that predicts a good response to neoadjuvant chemotherapy and that it is related with a good prognosis according to the Neo-Bioscore. Brachyury was significantly associated with estrogen receptor positive and human epidermal growth factor receptor 2 negative status; further study would be needed to clarify how it affects treatment prognosis.

Single-Incision, Gasless, Endoscopic Trans-Axillary Total Thyroidectomy: A Feasible and Oncologic Safe Surgery in Patients with Papillary Thyroid Carcinoma.

BACKGROUND: The aim of this study is to compare the feasibility and oncologic safety of Single-incision, gasless, Endoscopic trans-axillary bilateral Total thyroidectomy (SET) with open cervical total thyroidectomy in patients with papillary thyroid carcinoma (PTC). MATERIALS AND METHODS: From March 2008 to December 2012, PTC patients underwent bilateral total thyroidectomy. Conventional, open surgery was performed on 538 patients (Group O) and endoscopic surgery was performed on 200 patients (Group E). We analyzed the patient's clinicopathologic, postoperative complications, and surgical completeness. RESULTS: The mean ages of the patients were 48.9 ± 0.5 (range = 24-77) in Group O and 39.5 ± 0.8 (range = 17-73) in Group E with statistical significance (P < .001). Percentage of female patients were 74.3% in Group O and 96.0% in Group E with statistical significance (P < .001). The postoperative hospital stay in Group O was significantly longer than Group E (4.60 ± 0.05 versus 3.30 ± 0.05; P < .001). The operation time in Group E was significantly longer than Group O (93.9 ± 1.3 versus 142.6 ± 3.3; P < .001). More transient hypocalcemia was found in Group O compared to Group E with statistical significance (28.1% versus 22.4%; P < .001). There were no significant differences with respect to permanent hypocalcemia, permanent recurrent laryngeal nerve palsy, seroma, and hematoma. The mean 1 year-stimulated sTg was 0.23 ± 0.03 and 0.18 ± 0.02 in Group O and E, respectively. Tumor recurrence during short-term follow-up at neck ultrasonography (1 year) was detected in 4 patients in Group O. CONCLUSION: SET is safe and effective, not only for low-risk patients with early-detected cancer, but also for selected cases of advanced cancer.

Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer. METHODS: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed. RESULTS: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+. CONCLUSION: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.

Risk factors associated with high thyroglobulin level following radioactive iodine ablation, measured 12 months after treatment for papillary thyroid carcinoma.

PURPOSE: The measurement of serum thyroglobulin (Tg) of papillary thyroid carcinoma patients, 12 months after total thyroidectomy and radioactive iodine (RAI) ablation following thyroxine hormone withdrawal (T4-off Tg) or recombinant human thyroid-stimulating hormone stimulation (rhTSH-Tg), is standard method for monitoring disease status. The aim of this study was to find predictive factors for detectable T4-off Tg during follow-up. METHODS: A retrospective review was conducted of 329 patients who underwent total thyroidectomy and RAI ablation between October 2008 and August 2012. Subjects were assigned to high (>1 ng/mL, n = 53) and low (≤1 ng/mL, n = 276) groups, based on T4-off Tg measured 12 months postoperatively. Demographic and clinicopathological characteristics at diagnosis and follow-up were compared between the 2 groups. RESULTS: The low and high T4-off Tg groups differed with respect to tumor size, preoperative Tg, ablative Tg, cervical lymph node metastasis, thyroglobulinemia out of proportion to results of diagnostic whole body scan, and American Thyroid Association 3-level stratification and restratification. Multivariate analysis confirmed that ablative Tg > 1.0 ng/mL (odds ratio [OR], 10.801; P = 0.001), more than 5 cervical lymph node metastasis (OR, 6.491; P = 0.003), and thyroglobulinemia out of proportion (OR, 9.221; P = 0.000) were risk factors. CONCLUSION: Ablative Tg >1.0 ng/mL, more than 5 cervical lymph node metastasis, and thyroglobulinemia out of proportion were independent factors for T4-off Tg >1 ng/mL 12 months postoperative. In low-risk patients without these risk factors, the possible omission of Tg measurements could be considered during follow-up.

A comparison of postoperative pain after conventional open thyroidectomy and single-incision, gasless, endoscopic transaxillary thyroidectomy: a single institute prospective study.

PURPOSE: The aim of this study was to compare postoperative pain between single-incision, gasless, endoscopic transaxillary thyroidectomy (SET), and conventional open thyroidectomy. METHODS: From March to December 2015, patients with thyroid disease underwent total thyroidectomy or lobectomy. Patient's clinical and pathological characteristics, postoperative pain score using visual analog scale (VAS) were compared between the 2 groups. The primary endpoint was postoperative pain evaluated by VAS score and postoperative analgesic use. Operation time and length of postoperative hospital stay were secondary outcome measures. RESULTS: Conventional, open cervical surgery was performed on 30 patients (group O) and SET was performed on 27 patients (group E). Pain scores in shoulder area, which is the ipsilateral side of the tumor location at 1 hour and 24 hours after surgery, were higher in group E patients (P < 0.05). Pain scores 7 days after surgery did not differ between the 2 groups according to the locations (P < 0.05). CONCLUSION: In conclusion, endocrine surgeons should be concerned about immediate higher postoperative pain scores in patients who undergo SET.

Clinicopathologic significance of androgen receptor expression and discordant receptor status during progression in breast cancer.

The role of androgen receptor (AR) as a prognostic marker has been proposed in breast cancer. This study investigated AR status and its clinical significance in breast cancer, especially in triple negative breast cancer (TNBC). We also evaluated discordant AR status during the process of lymph node metastasis, locoregional recurrences (LRR) and distant metastasis. From January 2005 to December 2010, we retrospectively reviewed 120 patients including 55 TNBC patients diagnosed as invasive carcinoma with no special type (NST), who were treated at the Kangbuk Samsung Hospital. Tissue microarray was constructed and immunohistochemical expression of AR was performed for 120 invasive carcinomas, NST specimens and matching samples from 28 lymph node metastasis, 2 LRR and 8 distant metastases. AR expression was found in 35.0% (42/120) of the total patients and 14.5% (8/55) of those diagnosed as TNBC. Positive expression of AR was significantly correlated with smaller tumor size, early T stage, fewer lymph node metastases, early AJCC stage, lower histologic grade, estrogen receptor/progesterone receptor positivity, more luminal A type, less TNBC, longer disease-free survival and overall survival, fewer distant metastasis and no deaths from breast cancer (all P < 0.05). AR was a favorable prognostic marker for disease free survival in univariate analysis (P = 0.041). The discordance rate of AR status between primary and recurrent/metastatic disease was 21.6%. AR expression was associated with favorable clinicopathological outcomes in the whole study population. AR status can be altered during tumor progression.

High Expression of Urokinase-Type Plasminogen Activator Is Associated with Lymph Node Metastasis of Invasive Ductal Carcinoma of the Breast.

PURPOSE: In the present study, we evaluated the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) by performing immunohistochemical staining to determine whether they were reliable prognostic markers in patients with breast cancer. METHODS: Demographic and clinicopathological parameters of 214 patients with invasive ductal carcinoma (IDC) and 80 patients with ductal carcinoma in situ (DCIS) who were diagnosed and treated from 2006 to 2010 were analyzed. Tissue microarray was constructed and immunohistochemical staining was performed for each specimen. RESULTS: Univariate analyses showed that age at diagnosis, history of hormone replacement therapy, radiation therapy, skin and chest wall invasion, Paget disease, lymphovascular invasion, estrogen receptor positivity, and triple-negative subtype were significantly associated with patient prognosis (p<0.005). Patients with DCIS showed higher PAI-1 expression than patients with IDC (82.5% and 36.2%, respectively; p=0.012). Lymph node metastasis was more frequent in patients with high uPA levels than in patients with low uPA levels (p=0.001). CONCLUSION: Our results suggested that PAI-1 was involved in tumor progression in the early stages of breast cancer, such as DCIS. In addition, our results suggested that high uPA levels were associated with the lymph node metastasis of IDC.